[Clinical, radiological and molecular diagnosis of autosomal dominant Larsen syndrome: report of a large Iranian family]

ABSTRACT

Larsen syndrome [LS] is one of the rare autosomal dominant chondrodystrophias, characterized by multiple dislocations of the large joints, midfacial hypoplasia, and cleft palate. Recently it has been known that some missense mutations or small in-frame deletions in the gene Filamin B [FLNB] may cause autosomal dominant Larsen syndrome. Filamin B gene encodes a very important cytoskeletal protein named filamin B. This protein has central role on development of inter-cellular connective tissue, joint cartilage, and vertebral segmentation and development. In this article, we report a large Iranian pedigree including about 30 affected individuals to autosomal dominant Larsen syndrome in four subsequent generations. After ascertaining Larsen syndrome by clinical and radiological studies, in some of the available individuals of different branches of the pedigree, molecular analysis by dHPLC, direct sequencing, and endonuclease digestion methods have been carried out to detect responsible mutations in filamin B gene. We detected a point mutation on nucleotide 679 [679G>A] leading to substitution of glutamic acid instead of lysine in amino acid number 227 [E227K]. The mutation is one of the recurrent missense mutations that have been reported before in several families. In this pedigree, we found variable phenotypes according to the severity and spectrum of the symptoms